艾灸通过成纤维细胞生长因子受体1和血管内皮细胞生长因子受体2抑制肉瘤微环境血管生成

Moxibustion inhibits growth of tumor by down-regulating expression of FGFR1 and VEGFR2 in mice with sarcoma

目的:观察艾灸对肉瘤微环境中成纤维细胞生长因子受体1(FGFR1)和血管内皮细胞生长因子受体2(VEGFR2)的影响,探讨艾灸防治肉瘤的作用机制。方法:将接种S180肉瘤细胞形成移植瘤的C57BL/6J小鼠分为模型组、顺铂组和艾灸组,每组10只。艾灸组直接灸移植瘤,距离3 cm,10 min/次,每日1次,治疗14 d;顺铂组按照小鼠体质量给予腹腔注射顺铂(4μg/g),每日1次,治疗3次。治疗后称量移植瘤的重量;采用Luminex液相悬浮芯片检测血清血管内皮生长因子(VEGF)、FGFR1和VEGFR2含量;免疫组织化学法检测移植瘤VEGF的蛋白表达;荧光原位杂交技术检测移植瘤FGFR1和VEGFR2的基因表达。结果:与模型组比较,艾灸组和顺铂组均可抑制S180肉瘤的生长(P<0.001);艾灸组与顺铂组抑制肉瘤生长的作用差异无统计学意义(P>0.05)。与模型组比较,艾灸组移植瘤微环境可见大量的红细胞,VEGF阳性表达下降(P<0.01);与模型组比较,顺铂组红细胞无增多,VEGF阳性表达无改变(P>0.05);与顺铂组比较,艾灸组见大量的红细胞,VEGF阳性表达下降(P<0.05)。与模型组比较,艾灸组血清VEGF、VEGFR2和FGFR1的含量降低(P<0.01,P<0.05);与顺铂组比较,艾灸组血清VEGF、VEGFR2和FGFR1的含量明显下降(P<0.01,P<0.05)。与模型组比较,艾灸组FGFR1、VEGFR2基因的表达降低(P<0.001)。结论:艾灸可降低肉瘤微环境中FGFR1和VEGFR2的表达,抑制血管生成,从而控制肉瘤的生长。

Objective To observe the effect of moxibustion on the growth of tumor and expression of fibroblast growth factor receptor 1(FGFR1) and vascular endothelial cell growth factor receptor 2(VEGFR2) in mice with sarcoma, so as to explore its mechanisms underlying inhibiting sarcoma growth.Methods C57 BL/6 J mice(half male and half female) were inoculated with S180 sarcoma cells to form transplanted tumors, and divided into model control, medication and moxibustion groups, with 10 mice in each group. Moxibustion was applied to the transplanted tumor directly for 10 min, once a day for 14 days. After the treatment, Luminex liquid suspension chip was used to detect the contents of serum vascular endothelial growth factor(VEGF), FGFR1 and VEGFR2. The weight of the transplanted tumor was measured, and the expression of VEGF in the transplanted tumor was detected by immunohistochemistry, and the expression of FGFR1 and VEGFR2 mRNAs in the transplanted tumor was detected by fluorescence in situ hybridization.Results The tumor weight, VEGF immunoactivity, serum VEGF, VEGFR2 and FGFR1 contents, and expression levels of VEGFR2 and FGFR1 mRNAs in the transplanted tumor were significantly lower in the moxibustion group than in the model group(P<0.001, P<0.01, P<0.05). Compared with the model group, the tumor weight was remarkably lower in the medication group(P<0.001). Compared with the medication group, th VEGF immunoactivity and the contents of serum VEGF, VEGFR2 and FGFR1 were significantly lower in the moxibustion group(P<0.01, P<0.05). H.E. staining showed a large number of red blood cells were observed in the microenvironment of the transplanted tumor in the moxibustion group rather than in the medication group.Conclusion Moxibustion can inhibit the growth of tumor in mice with sarcoma, which may be related to its function in reducing the expression of FGFR1 and VEGFR2 to inhibit angiogenesis.